IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets

Stefan Stojkovic; Åsa Thulin; Lena Hell; Barbara Thaler; Sabine Rauscher; Johanna Baumgartner; Marion Gröger; Cihan Ay; Svitlana Demyanets; Christoph Neumayer; Ihor Huk; Andreas Spittler; Kurt Huber; Johann Wojta; Agneta Siegbahn; Mikael Åberg

doi:10.1160/TH16-10-0784

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2017; 117(07): 1379-1390
DOI: 10.1160/TH16-10-0784

Coagulation and Fibrinolysis

Schattauer GmbH

IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets

Stefan Stojkovic

¹Department of Internal Medicine II, Medical University of Vienna, Austria

,

Åsa Thulin

²Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden

,

Lena Hell

³Department of Internal Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, Austria

,

Barbara Thaler

¹Department of Internal Medicine II, Medical University of Vienna, Austria

,

Sabine Rauscher

⁴Core Facilities, Medical University of Vienna, Austria

,

Johanna Baumgartner

¹Department of Internal Medicine II, Medical University of Vienna, Austria

,

Marion Gröger

⁴Core Facilities, Medical University of Vienna, Austria

,

Cihan Ay

³Department of Internal Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, Austria

,

Svitlana Demyanets

⁵Department of Laboratory Medicine, Medical University of Vienna, Austria

,

Christoph Neumayer

⁶Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria

,

Ihor Huk

⁶Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria

,

Andreas Spittler

⁴Core Facilities, Medical University of Vienna, Austria

⁶Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria

,

Kurt Huber

⁷3rd Medical Department for Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria

⁸Sigmund FReud Private University, Medical School, Vienna, Austria

,

Johann Wojta

¹Department of Internal Medicine II, Medical University of Vienna, Austria

⁴Core Facilities, Medical University of Vienna, Austria

⁸Sigmund FReud Private University, Medical School, Vienna, Austria

⁹Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Austria

,

Agneta Siegbahn

²Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden

,

Mikael Åberg

²Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden

› Author Affiliations

Abstract

Summary

Monocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and concentration-dependent increase of monocyte TF mRNA and protein levels via binding to the ST2-receptor and activation of the NFκB-pathway. The IL-33 treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the TF activity of both the isolated monocytes and monocyte-derived MVs. The monocytes were classified into subsets according to their CD14 and CD16 expression. Intermediate monocytes (IM) showed the highest ST2 receptor expression, followed by non-classical monocytes (NCM), and classical monocytes (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma levels of IL–33 were positively correlated with CD14+TF+ MVs in patients undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide novel evidence that the proinflammatory cytokine IL-33 induces differential TF expression and activity in monocyte subsets, as well as the release of procoagulant MVs. In this manner, IL-33 may contribute to the formation of a prothrombotic state characteristic for cardiovascular disease.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Interleukin-33 - tissue factor - monocyte subsets - microvesicles - thrombosis

Full Text

References

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